Thiopurine Methyltransferase Genotype Predicts Therapy-Limiting Severe Toxicity from Azathioprine

A.J. Black, Howard McLeod, HA Capell, RH Powrie, LK Matowe, Stuart C Pritchard, Elaina Susan Renata Collie-Duguid, David M Reid

Research output: Contribution to journalArticle

336 Citations (Scopus)

Abstract

Background: Substantial hematologic toxicity limits the use of azathioprine.

Objective: To evaluate 1) polymorphic inactivation of azathioprine by thiopurine methyltransferase and 2) clinical toxicity.

Design: Prospective cohort study.

Setting: Two rheumatology units.

Patients: 67 patients for whom azathioprine was prescribed as second-line therapy for rheumatic disease.

Measurements: Polymerase chain reaction-based assays were used to detect mutations in thiopurine methyltransferase. The primary end point was discontinuation of azathioprine therapy because of toxicity.

Results: Six of 67 patients (9%) were heterozygous for mutant thiopurine methyltransferase alleles. Five of the 6 patients discontinued therapy within 1 month of starting treatment because of low leukocyte counts. The sixth patient did not adhere to treatment. Patients with wild-type thiopurine methyltransferase alleles received therapy longer than did patients with mutant alleles (median duration of therapy, 39 weeks [range, 6 to 180 weeks] and 2 weeks [range, 2 to 4 weeks], respectively; P = 0.018).

Conclusion: Analysis of thiopurine methyltransferase genotype is a quick way to identify patients at risk for acute toxicity from azathioprine.

Original languageEnglish
Pages (from-to)716-718
Number of pages3
JournalAnnals of Internal Medicine
Volume129
Issue number9
Publication statusPublished - 1 Nov 1998

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